Outcomes in Relation to Early Parenteral Nutrition Use in Preterm Neonates Born between 30 and 33 Weeks Gestation: A Propensity Score Matched Observational Study

Abstract

Importance: Preterm neonates are among the highest users of parenteral nutrition (PN). Randomised trials in critically ill older children show that harms, such as nosocomial infection, outweigh benefits of early PN administration; there is a paucity of similar randomised trial data in neonates. Objective: To evaluate whether in preterm neonates born between 30+0 and 32+6 weeks+days, PN use in the first seven postnatal days, compared with no PN use, is associated with differences in survival and other important morbidities. Design: Retrospective cohort study using propensity matching including 35 maternal, infant and organisational factors to minimise bias and confounding. Routinely recorded clinical data obtained from the UK National Neonatal Research Database. Setting: National population-level data from all National Health Service neonatal units in England and Wales. Participants: 35,362 neonates born over the period January 2012 to December 2017 and admitted to a neonatal unit; 16,292 neonates were compared in propensity score matched analyses. Exposure: The exposure was PN administered in the first seven days of postnatal life; the comparator was no PN in the first seven days. Main Outcome and Measure: The primary outcome was survival to discharge from neonatal care. Secondary outcomes comprised the neonatal core outcome set (including necrotising enterocolitis, bronchopulmonary dysplasia and late-onset sepsis). Results: Compared with matched neonates not given PN in the first postnatal week, neonates who received PN had higher survival to discharge (absolute rate increase 0.91%; 95% CI 0.53% to 1.30%), but higher rates of necrotising enterocolitis (absolute rate increase 4.6%; 95% CI 3.9% to 5.3%), bronchopulmonary dysplasia (absolute rate increase 3.9%; 95% CI 3.2% to 4.7%), late-onset sepsis (absolute rate increase 1.5%; 95% CI 1.1% to 1.8%) and need for surgical procedures (absolute rate increase 0.92%; 95% CI 0.57% to 1.3%). Conclusions and Relevance: In neonates born between 30+0 and 32+6 weeks gestation, those given PN in the first postnatal week had higher rates of survival but higher rates of important neonatal morbidities. Prospective, randomised trials powered for important outcomes are needed to identify in which neonates the benefits of early PN use outweigh the harms. Trial Registration: ClinicalTrials.gov: NCT03767634, Prospectively Registered: 06/12/2018. Funding Statement: The NNRD is funded and maintained from awards to NM. These include costs for data transfer, storage, cleaning, merging, administration and regulatory approvals. The extraction of study data from the NNRD and analysis for this study was funded through a Mason Medical Research Fellowship awarded to JW. CG was funded by the United Kingdom Medical Research Council (MRC) through a Clinician Scientist Fellowship award. Declaration of Interests: JW has received support from Chiesi Pharmaceuticals to attend an educational conference and has received a research grant from Mason Medical Research Foundation. SU has received funding from the National Institute of Health Research, the Department of Health and Prolacta Life Sciences. SU has been on the Advisory Board of Fresenius Kabi and received honoraria and travel expenses for speaking at study days organised by Fresenius Kabi. SU is a member of the National Institute for Health and Care Excellence Parenteral Nutrition Guideline Development Committee. NM is the Chief Investigator for the National Neonatal Research Database and Director of the Neonatal Data Analysis Unit at Imperial College London. In the last five years NM has served on the Board of Trustees of the Royal College of Paediatrics and Child Health, David Harvey Trust, Medical Women’s Federation and Medact; and is a member of the Nestle Scientific Advisory Board. NM has received research grants from the British Heart Foundation, Medical Research Council, National Institute of Health Research, Westminster Research Fund, Collaboration for Leadership in Applied Health and Care Northwest London, Healthcare Quality Improvement Partnership, Bliss, Prolacta Life Sciences, Chiesi, Shire and HCA International; travel and accommodation expenses from, Nutricia, Prolacta, Nestle and Chiesi; honoraria from Ferring Pharmaceuticals and Alexion Pharmaceuticals for contributions to expert advisory boards, and Chiesi for contributing to a lecture programme. CG is part of an international team developing reporting guidance (a CONSORT extension) for clinical trials using cohorts and routinely collected health data. He has received support from Chiesi Pharmaceuticals to attend an educational conference; in the past 5 years he been investigator on received research grants from Medical Research Council, National Institute of Health Research, Canadian Institute of Health Research, Department of Health in England, Mason Medical Research Foundation, Westminster Medical School Research Trust and Chiesi Pharmaceuticals, and has been an unremunerated member of the Neonatal Data Analysis Unit Board, which oversees the NNRD. The authors declare no other competing interests. Ethics Approval Statement: Obtained study-specific research ethics committee, Health Research Authority and Health and Care Research Wales approval (18/NI/0214).